Regulating Mammalian Target of Rapamycin To Tune Vaccination-Induced CD8+ T Cell Responses for Tumor Immunity
- 1 April 2012
- journal article
- Published by The American Association of Immunologists
- Vol. 188 (7), 3080-3087
- https://doi.org/10.4049/jimmunol.1103365
Abstract
Vaccine strategies aimed at generating CD8+ T cell memory responses are likely to show augmented efficacy against chronic challenges like tumor. The abundance in variety of memory CD8+ T cells behooves development of vaccine strategies that generate distinct memory responses and evaluate them for tumor efficacy. In this study, we demonstrate the ability of a variety of rapamycin treatment regimens to regulate virus vaccination-induced CD8+ T cell memory responses and tumor efficacy. Strikingly, a short course of high-dose, but not low-dose, rapamycin treatment transiently blocks viral vaccination-induced mammalian target of rapamycin activity in CD8+ T cells favoring persistence and Ag-recall responses over type 1 effector maturation; however, prolonged high-dose rapamycin administration abrogated memory responses. Furthermore, a short course of high-dose rapamycin treatment generated CD8+ T cell memory responses that were independent of IL-15 and IL-7 and were programmed early for sustenance and greater tumor efficacy. These results demonstrate the impact a regimen of rapamycin treatment has on vaccine-induced CD8+ T cell responses and indicates that judicious application of rapamycin can augment vaccine efficacy for chronic challenges.Keywords
This publication has 40 references indexed in Scilit:
- A Central Role for mTOR Kinase in Homeostatic Proliferation Induced CD8+ T Cell Memory and Tumor ImmunityImmunity, 2011
- The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2Nature Immunology, 2011
- The S1P1-mTOR axis directs the reciprocal differentiation of TH1 and Treg cellsNature Immunology, 2010
- Diversity in T Cell Memory: An Embarrassment of RichesImmunity, 2009
- mTOR regulates memory CD8 T-cell differentiationNature, 2009
- Enhancing CD8 T-cell memory by modulating fatty acid metabolismNature, 2009
- The mTOR Kinase Differentially Regulates Effector and Regulatory T Cell Lineage CommitmentImmunity, 2009
- Inflammation Directs Memory Precursor and Short-Lived Effector CD8+ T Cell Fates via the Graded Expression of T-bet Transcription FactorImmunity, 2007
- Vaccination with NY-ESO-1 protein and CpG in Montanide induces integrated antibody/Th1 responses and CD8 T cells through cross-primingProceedings of the National Academy of Sciences, 2007
- mTOR and cancer: insights into a complex relationshipNature Reviews Cancer, 2006